An impressive new study from scientists at the University of Utah has described how an impaired immune system can alter the composition of the gut microbiome resulting in metabolic disease and obesity. Demonstrated in mouse experiments, the research suggests certain species of gut bacteria can prevent the gut from absorbing fat, pointing to exciting potential future anti-obesity therapies.

The research originated from an unexpected observation. Ongoing experiments in mice engineered to lack a gene called MyD88 surprisingly resulted in the animals gaining significant amounts of weight. The specific gene was being studied for its relationship to immune function in the gut. It was discovered that suppressing this gene resulted in lower production of immunoglobulin A (IgA) antibodies in the gut, but the real mystery was how this gut-related immune mechanism resulted in metabolic disease and obesity.

The hypothesis was that gut bacteria were playing some kind of role in modulating this interaction between immune activity and obesity. Eliminating the microbiome of these MyD88-blocked mice with antibiotics revealed the animals' metabolism returning to normal and becoming leaner. This affirmed a microbiome-related mechanism was playing a part, so the researchers set out to discover which bacterial populations could be responsible.

Two major observations quickly jumped out at the researchers. The obese mice showed greatly reduced numbers of Clostridia bacteria, a class of microbe consisting of several different particular species. On the other hand, an increase in the abundance of a bacterial species called Desulfovibrio was observed.

Subsequent studies with healthy mice revealed a solid causal connection between these gut bacterial species and obesity. Healthy mice became obese when they were colonized with this altered microbiome composition, and conversely, when Clostridia was reintroduced into the MyD88-blocked mice they lost weight and displayed metabolic improvements.

The study revealed that Clostridia bacteria seem to have the ability to regulate genes that direct the body to absorb dietary fats. Desulfovibrio bacteria, on the contrary, seemed to block the colonization of Clostridia, so essentially, more Desulfovibrio and less Clostridia equaled higher absorption of fats in the intestine. And modulating this delicate microbiome balance is the immune system.

But, how does this impressive volume of animal research translate to humans?

The researchers suggest initial observations in obese human subjects have revealed low levels of Clostridia. Immune dysfunction has also been observed in human subjects suffering from both obesity and type 2 diabetes. All of this goes to suggest that it is not unreasonable to hypothesize the mechanism explored in this study could apply to humans.

June Round, co-senior author on the new research, admits it is early days for the research and there are plenty more questions to be answered, such as exactly how Clostridia regulates gene expression in the gut.

"We've stumbled onto a relatively unexplored aspect of type 2 diabetes and obesity," says Round. "Now that we've found the minimal bacteria responsible for this slimming effect, we have the potential to really understand what the organisms are doing and whether they have therapeutic value."

Round says the ultimate goal would be to isolate the molecules that the bacteria releases to generate its anti-obesity effect. Homing in on the specific molecular mechanism at play could be a more effective and consistent therapeutic option than simply administering Clostridia probiotics. Direct microbiome alterations will not work for everyone, Round says, due to the large array of factors that influence bacterial activity in different individuals.

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With interests in film, new media, and the new wave of psychedelic science, Rich has written for a number of online and print publications over the last decade and was Chair of the Australian Film Critics Association from 2013-2015. Since joining New Atlas Rich’s interests have broadened to encompass the era-defining effects of new technology on culture and life in the 21st century.

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